Chronic leg ulceration significantly impacts on the individual's health status. It is also a major financial burden on the national healthcare system. the maintenance of chronic ulcer is the result of an equilibrium imbalance between local tissue demand and systemic metabolic supply. the effect of this pathological condition leads to an increase in free radical production overwhelming the scavenging capacity of physiological antioxidant defence mechanisms. the reduction of oxygen free radicals concentration removes one of the major causes hindering the healing of chronic ulcer. Blood ozonation is recognised to induce a strong oxidative stress which causes an oxidative preconditioning that increases the efficacy of endogenous oxygen free radicals' scavenging properties. after a brief review of the pathophysiology of cicatrization and ozone properties, we document a significant number of patients who did not respond to conventional treatment, yet were successfully cured with major ozonated autohaemotherapy.